Fluorine-Containing Synthons

Subject Index

Downloaded by 80.82.78.170 on December 6, 2016 | http://pubs.acs.org Publication Date: July 21, 2005 | doi: 10.1021/bk-2005-0911.ix002

A

Adducts with CF group, Michael addition products, stereochemistry, 404-405 Alcohols-sulfur pentafluoro compounds, preparation, 95-96f Aldehydes-sulfur pentafluoro compounds, preparation, 95-96/ Aldol reaction. See Mukaiyama-aldol reaction Aliphatic hydrocarbons-sulfur pentafluoro compounds, preparation, 94-95 Alkanes-sulfur pentafluoro compounds, preparation. See Aliphatic hydrocarbons Alkenes-sulfur pentafluoro compounds, preparation. See Aliphatic hydrocarbons Alkoxide-induced trifluoromethylation, trifluoromethyl phenyl sulfones/sulfoxide, 36-41 Alkoxide-mediated trifluoromethylation and difluoromethylenation, mechanism, 44/ Alkoxides-sulfur pentafluoro compounds, preparation, 95-96/ Alkyl/fluoroalkyl halides, sulfur pentafluoro-, preparation, 92-93 Alkyl side chains in fluoroalkylated alkynes, synthesis, 193 Alkynes fluorine-containing, synthesis and applications, 190-203 sulfur pentafluoro compounds, preparation (See Aliphatic hydrocarbons) Aliènes, mono- and di-fluorinated, functionalized, 204-215 3

Abramovitch adaptation, Fischer indole synthesis, 306 Absolute configuration, efficiency, carboxypeptidase Y catalyzed peptide synthesis, 621 Acetals and ketals, optically active trifluoromethylated, preparation, 323 Acetals sulfur pentafluoro compounds, preparation, 95-96/ Acetone in direct aldol reaction with trifluoroacetaldehyde ethyl hemiacetal, 351-353/ Acetonitrile (MeCN), electrolytic solvent effects, 278 Acetylenes, fluoroalkylated, synthesis and applications, 190-203 Acid or base-catalyzed dehydrofluorination, difluorinated enol ethers, preparation, 457 Acrylate monomers with terminally SF -fluorinated side chains, preparation, 100-101 1 -Acyl-3-hydroxy-4-R p-lactams, enantiopure, synthesis, 552, 553/ N-Acyl-oxazolin-2-thione, ethyl trifluoropyruvate, titanium(IV) chloride catalyst, 574-575 Acylsilanes Brook and retro-Brook rearrangement, 378-379, 381-382,386, 389-390, 394-395 fluorinated, allylation reaction, 389-395 fluorinated, synthesis and utility, 378-398 5

r

641 Soloshonok; Fluorine-Containing Synthons ACS Symposium Series; American Chemical Society: Washington, DC, 2005.


642 /V-AUyl homoallyl amines, ring closing metathesis, 418,420/ Allylation reactions fluorinated acylsilanes, 389-395 trifluoromethyl homoallylic amines, 413-420/ with an aldimine, 416-417/ with zinc in DMF and THF, 414415/ Allylbenzene radical addition reaction with ethyl bromodifluoroacetate, 485-486/ Allylic alcohol, stereospecific fluorination, 176-177 Allylic difluoromethylenenephosphonate in thionucleotide analogs synthesis, 450 Allylicfluorides,optically active, synthesis, 175-178 Allylsilanes, electrophilic fluorodesilylation in allylic fluoride synthesis, 177-178 Allyltributyltin radical addition reaction with ethyl bromodifluoroacetate, 487-488/ Amides,fluorinated,Wittig reaction, 596 Amines, di-unsaturated, one-pot synthesis, 418-419/ Amines tofluorinatedalkynoates, Michael addition, 595 β-Amino acid derivatives, 7-member, ring-closing metathesis, 602604 Ainino acids carryingfluorinatedside chains, screening system applications, 625-631 difluorinated, synthetic application, 463-466 fluorinated, synthesis, 562-571 a-Amino ΛΓ-tert-butanesulfinimines, diastereoselective trifluoromethylation, 20

Anionic electron donors, selfassembly, 526-532 Anodic fluorination diastereoselective, of heterocycles, 284-286/ five-membered heteroaromatic compounds, 279-280/ heterocyclic compounds, 276-287 Anodicringfluorination,pyrrole derivative, 281-283/ Anti-Baldwin nucleophilic cyclizations, 270-271/ Antiestrogenic drug, panomifene, synthesis, 201-202/ Antiparallel homodimeric coiled coil peptide, screening system basis, 623-624/ Applications amino acid drugs (Captopril), 601 anion driven self-assembly, threecomponent heteromeric adducts, 531 conjugated polymers, 505 3,5-dichloro-2,4,6trifluoropyridine, 249 gem-difluorocyclopropanes, 430 fluoral, asfluorinatedsynthon, 368-376 fluorinated amino acids, 563 halogen bonding driven selfassembly, haloperfluorocarbons, 532538 α-hydroxy-P-amino acid moieties, 545 SF compounds, overview, 108113 Aromatic chemistry, sulfur pentafluoro compounds, 103-108 Aromatic compounds with fluoral, asymmetric Friedel-Crafts reactions, 365-366/ Aromatic substitution, regioselective, fluorine on polyfluorinated BINOLs, 291-292 5

Soloshonok; Fluorine-Containing Synthons ACS Symposium Series; American Chemical Society: Washington, DC, 2005.


643 Aromatics, magnesium-promoted selective defluorination, 462-463/ Aryl carbonyl compounds, enantioselective trifluoromethylation, 22 Arylglycidic esters, ring opening hydrofluorination, 181-182 Asymmetric catalysis polyfluorinated BINOLs application, 293-299/ with fluorinated synthons, 356367 Asymmetric cyclopropanation, 168169,184, 185/ Asymmetric hydrogénation reactions, 4-trifluoromethyl-L-proline synthesis, 564-565 Asymmetric synthesis, monofluorinated compounds, 173-189 ATCase inhibitors, potential, preparation, 444 Aza-Michael reactions adducts, elaboration into y[CH(CF )NH]Gly-peptides, 586 α-amino esters to N-(atrifluoromethyl)acryloyl-aamino, 587-588 in synthesis PMR i|/[NHCH peptides, 3,3,3trifluoroalamine mimic, 589 to y|KHCH(CF3)]-containing dipeptide units, 579 ψ[NHCH(CF3)]Gly-peptide backbone, 585 Aziridines and epoxides, optically active trifluoromethylated, preparation, 323-324 3

2]

Baeyer-Villiger reaction, 291, 370372

Baldwin's rules, 270 Balz-Schiemann (fluorodediazotization) fluorination, 263 Barbier conditions, allylation reactions, 414 Benzyl alcohols, nucleophilic fluorination, 181 Benzylicfluorides,derivatives, preparation, 180-186 Binaphthol ligands. See BINOL entries BINOL-derived titanium catalyst in carbonyl-ene reactions, 357360/ in Friedel-Crafts reactions, 362363t 364-365* BINOL-lanthanide complexes in asymmetric epoxidation reactions, 297-299/ BINOLs, fluorinated ligands, preparation, 289-291 BINOLs, polyfluorinated, application in asymmetric catalysis, 293299/ BINOLs, regioselective nucleophilic aromatic fluorine substitution on polyfluorinated, 291-292/ Biochemical resolution, racemates, 320 Biological activity, SF compounds, 109 Biologically important compounds, fluorine analogs, applications to synthesis, 489-491/ Biologically important imidazoles and indoles, selective fluorination, 303-316 Bipyridine system, polyfunctional, synthesis and reactions, 254 Bis(ethylsulfanyl) hexafluorobutene line, trifluoromethylated heterocycles, 241-245 Bis(ethylsulfanyl)-tetrafluoropropene line, trifluoromethylated heterocycles, 238-241 5


644 1,6-Bis(hydroxymethyl)-2,2,5,5tetrafluorobicyclopropane shape, MO's, 430-431 Bis(oxazoline) ligand in asymmetric cyclopropanation, afluorostyrene, 168-169 Bis-SF carbon compounds, 94-95 BMS-204352, enantioselective synthesis, 182, 183/ Boron Lewis acid and S(perfluoroalkyl)dibenzothiopheni urn triflate perfluoroalkylation, 5 Bromhydrins, cyclization, chiral compound configurations, 422424 Bromine and iodine, discrimination between, 224/ 226-227/ 1 -Bromo-1 -chloro-2,2,2trifluoroethane metallation, 147 a-Bromo-p,P-difluorostyrenes, synthesis, 148-149/ a-Bromo-P,p-difluorovinyl zinc reagent preparation, 148-149 Bromo-fluoropyridine building blocks, synthesis, 252-253 2-Bromo-3,3,3-trifluoropropene, in synthesis, trifluoromethylated acetylenes, 192-193/ Brook and retro-Brook rearrangements acylsilanes, 378-379, 381-382, 386, 389-390, 394-395 difluorinated enol ethers, preparation, 457-458/ Building block approach to difluoromethylenephosphonate function, 448-450/ Building block pentafluoropyridine in polyfunctional pyridines and macrocycles, 248-261 Building blocks, site-specific peptide and protein modification, fluorinated amino acid, 611635 Butyl acrylate, electrochemical trifluoromethylations, 12


5

C a

C ,a-dialkyl amino acid-4guanidinophenyl esters, synthesis, 616-619 C -fluoroalkyl substituted amino acids (racemic), enzymatic resolution, 612-615/ Cadmium reagent reaction with copper(I) chloride, phosphonate synthesis, 445 Cannizaro reaction, 37, 75 Carbene addition by Dolbier's procedure, 436 Carbinols with CF , generation, overview, 8-11 Carbometallation, fluoroalkylated alkynes, synthetic applications, 197-201 Carbon-fluorine bond cleavage, magnesium-promoted, 455-475 Carbon-fluorine bond formation in difluoromethylenephosphonate function, 447-448/ α-Carbon functional groups, stereospecific transformation, trifluoromethyl group, 325-333 Carbon-phosphorus bond formation, difluoromethylenephosphonate function, 446-447/ Carbonyl-ene reaction, catalytic enantioselective C-C bond formation, 357-361/ Carbonyl halides-sulfur pentafluoro compounds, preparation, 97100 Carbostannylation, fluoroalkylated alkynes, synthetic applications, 197-200 Carboxylic acid derivatives, sulfur pentafluoro compounds, preparation, 97-100 Carboxypeptidase Y catalyzed peptide synthesis, α-fluoroalkyl amino acids, 619-621 a

3


645

Catalysis. See Asymmetric catalysis; reaction entries Catalytic pathway for production of (triflluoromethyl)silanes, 35-36/ Catalytic trifluoromethylation, 22-24 Cerium(III) salts, carbanion reactivity modulation, 443,444 Cesium fluoride, trifluoromethylation catalyst, 76-79 CF H. See Trifluoromethane Charge-transfer interactions in intermolecular synthons, 499 Chemical stability, SF compounds, 110 Chiral α-carbon, building methods to trifluoromethyl group and substitutions, 318-341 Chiral carbon center, trifluoromethylated, construction, 320-324 Chiral carbon without hetero atom, optically active trifluoromethylated compounds, 324 Chiral enamine, reaction with trifluoroacetaldehyde ethyl hemiacetal, 351 Chiral β-enamino esters, reduction, stereochemical outcome, 600-601 Chiral imide enolates, diastereoselective trifluoromethylation, 12 Chiral imines, reaction with trifluoroacetaldehyde ethyl hemiacetal, 348-350* Chlorine vs. trialkylsilyl, protective group comparison, 227-229/ Chlorins, direct trifluoromethylation, 5 a-Chloro-β,β -difluorostyrenes, synthesis, 145-148* a-Chloro- β,β -difluorovinyl zinc reagent preparation, 145-148 4-(p-Chlorophenylthio)methyl-1,3dioxolan-2-one, anodic fluorination, 285/


3

5

Chromium carbonyl in dehydroxyfluorination indanols and tetralols, 181 Cieplak rule in stereoselection, Michael addition reactions of enolates, 408-409 Cinnarizine analog preparation, 6970/ Claisen rearrangement, fluorinated allyl vinyl ethers, 468 Co-crystal formation, perfluoroalkyl iodides with aromatic/aliphatic diamines, 516-517/ Cobalt(III)/zinc bimetallic redox system, primary phosphonates synthesis, 445 Coiled coil based screening system, 623-625 Coiled coil structure motif, 622-623 Conformational features, PMR y[NHCH(CF )]Gly-peptides, 582-584 Copper catalysts acetoacetate, in olefin methathesis reaction protocol, 436/437 asymmetric cyclopropanation, afluorostyrene, 168-169 carbocupration, fluoroalkylated alkynes, synthetic applications, 200-201 cuprous halide, fluorovinylzinc reagents with allyl halides, 137,139/ cyclopropanation, afluorostyrene, 184, 185/ mediated reactions, ethyl bromodifluoroacetate, 476495 phosphonate preparation, 445 salts, for construction, fluorinated cyclopropanecarboxylates, 166 "Core scaffold" fimctionalization strategy, 251 Cotton effect, 431 3


646 Cross-coupling reactions 4,4-difluoro- α-tocopherol, synthesis, 489-490 ethyl bromodifluoroacetate, organocopper iodide complex formed, 478-481 monofluoroalkene stereoselective synthesis, 120-134 SF aromatic compounds, preparation, 104 Crystal engineering fluorine-based, 498-513 halogen bonding-based, 514-542 Crystal packing in solid-state UVinitiated polymers, fluoro synthons, 509-510 Crystal packing motifs,fluorohybrid synthons, 503-505 Curtius degradation, 166-167, 185 α-Cyano-a-fluoro-p-tolylacetic acid, resolution methods, 184 2-Cyano-l-methylpyrrole, anodic fluorination, 281-282/ Cycloadditions, vinyl fluorides, 155172 Cyclopropanations, vinyl fluorides, 164-170 Cytotoxicity,fluoro-taxoids,558


5

D Dane's diene in Diels-Alder reactions withfluorinatedp-benzoquinones, 163-164 Danishefsky's diene, fluorinated analog, preparation, 460 DCTFA, industrial synthetic application as fluorinated synthon, 368-376 Dehydroiodination in vinyl iodides, 193 Dehydroxy-fluorination, indanols and tetralols, chromium carbonyl stereocontrol, 181

Density Function Theory. See DFT calculations Deprotonation-triggered heavy halogen hopping, 223-224/ Dess-Martin conditions for oxidations, 210-211 DFA (1,1-Difluoroallene), synthetis and cycloaddition chemistry, 205-207 DFT calculations formation of di-substituted anti1,3-diol, 45-46 interaction dissociation energy, I anion complex, 527 Diacetylene function in designed hybrid fluoro synthons, 506508/ UV-mitiated photopolymerizations, 508510 Diastereofacial selection, fluorinecontaining methyl groups, role, 399-411 Diastereoselective animations, 323 Diastereoselective anodic fluorination, heterocycles, 284-286/ Diastereoselective trifluoromethylation with (trifluoromethyl)-trimethylsilane, 18-21 3,3-Dichloro-1,1,1 -trifluoroacetone. See DCTFA 3,5-Dichloro-2,4,6-trifluoropyridine herbicide precursor, 249 Dichlorocarbene reactions with fluorostyrenes, 164-165 Dichloromethane solvent effects, 279 solvent for olefin methathesis reaction protocol, 435 solvent influence on stereoselectivity in pseudo peptide synthesis, 579 Diels-Alder reactions. See also RetroDiels-Alder reaction


3


647 adduct formation with butadiene, synthesis, 380-382* 93 gem-Difluoroalkenes, intramolecular cycloadditions, 207 vinylic substitution, 262-275 enantioselective hetero, 461 Difluoroallenes, functionalized, 207open-chain dienes, 283/ 210 vinyl fluorides, 157-164 Difluoroallenyl indium intermediate, with a-fluoro-a,P-unsaturated 207-208 carbonyl compounds, 159— Difluorocarboxylate anions, 164 generation and uses, 72-74/ Dienyl and polyunsaturated allylic gem-Difluorocyelopropanes fluorides, preparation, 179-181 multi, synthesis, 434-437 Diethyl optically active, synthesis, 432434/ difluorophosphonomethyldithioac etate in functionalized thiazolines, 2,2-Difluoroenol silyl ether 449-450/ halogenation, 50-52 Diethyl 2-OXO-, 1,1Difluoroenol silyl ethers and difluoroethylphosphonate hydrate derivatives, selective C-F bond in difluoroallylic phosphonates, cleavage, 455-475 449 Difluoroenoxysilanes, electrophilic 0,0-Diethyl halogenation, 384 phosphonodifluoromethyllithium Difluoroketene aminals, nucleophilic reagent, 442- 444 intermediates, 72-74/ Diethylzinc addition to aldehydes, Difluoromethyl ketones, magnesiumapplication in asymmetric promoted selective defluorination, synthesis, 294 461-462 Difluorinated enol ethers and Difluoromethyl phenyl sulfone in derivatives, preparation, 456-458/ difluoromethylation and α,α-Difluoro fatty acid analog, difluoromethylenation, 41-49 Difluoromethyl phenyl sulfones, use synthesis by radical reaction, in difluoromethylenation, 42490-491/ α,α-Difluoro-a-halo49 Difluoromethylene-bisphosphonates, acetyltrialkylsilanes, synthesis, phosphonoacetates in fluorinated 384 phosphate analogs preparation, 3.3-Difluoro-2,4-pentane diolate 448-449 dianion as model for DFT Difluoromethylene groups, calculations, 45 introduction byfluorinatedsilyl 4.4-Difluoro-a-toeopherol, synthesis enol ethers, 49-52 by cross-coupling reaction, 489Difluoromethylenephosphonate 490 function construction, 446-448/ l,l-Difluoro-2-trialkylsilyl-2building block approach, 448trialkylsilyloxyethenes, synthesis, 450/ 382-383* Difluoromethylenephosphonate unit, Difluoroacetyltrialkylsilanes direct introduction during reaction with sulfur ylides, 388synthesis, 441-446/ 389/



648

2- and 4-Difluoromethylimidazole, synthesis by deoxyfluorination, 308-309 Difluoromethylphosphonates, general synthetic methods, 440-454 3.3-Difluoroproline synthesis, 566567/ a«tf-2,2-Difluoropropan-1,3-diols, stereoselective preparation, 42-51 2,2-Difluoropropan-l,3-diols with stereoselectivity, synthetic applications, 47-49 4.4-Difluoropyroglutamic acid derivative, preparation, 568 β, β-Difluorostyrenes with sp carbon nucleophile, cyclization, 269-270 with sp nitrogen nucleophile, cyclization, 267-269/ with sp carbon nucleophile, cyclization, 266-267 with sp heteroatom nucleophile, cyclization, 265-266/ 271 gem-Difluorostyrenes with sp heteroatom nucleophile, cyclization, 272 1,2-Dimethoxyethane. See DME Dimethyl formamide. See DMF Dimethyl sulfoxide. See DMSO 2.2- Dimethylchroman-4-ones, fluorinated analog synthesis, 24 anii-1,3-Diol functionality, fundamental unit in naturally occurring compounds, 42 Diphenyl disulfide in terf-butoxide induced trifluoromethylation, 40 1.3-Dipolar cycloaddition, dithiocarboxylic derivatives, dimethylacetylendicarboxylate, 243-245 Direction-reversal strategy, 578 Disubstituted SF benzene derivative, preparation, 104 2

2

3

3

3

5

Dithiocarboxylic derivatives with dimethylacetylendicarboxylate 1,3 -dipolar cycloaddition, 243-245 Diversity Oriented Synthesis (DOS), 218-231,250-251 Dixon's method, 140 DME (1,2-dimethoxyethane), solvent effects, 278-279/ DMF (Ν,Ν-dimethyl formamide) CF reservoir provider, 61-63 solvent for allylation reaction, 414-415t solvent in trifluoromethylations, 8-11 DMSO solvent for trifluoromethylation, 38 solvent in Michael-type 1,4addition reactions, ethyl bromodifluoroacetate, 481482 Dolbier's reagent and method, 72-73 Domains, perfluorinated, segregation in crystal lattice, 258-259/ DOS. See Diversity Oriented Synthesis DuPont Merck's MMP inhibitors and CF -analogs, 573-574/ 3

3

Egyptian cotton leaf worm, synthesis ofpheromone, 130 Electrochemical trifluoromethylations, butyl acrylate, 12 Electron-conducting polymer design, conjugated polymers, fluorinecontaining hybrids, 505-507/ Electronic effects, single fluorine substituent in simple vinyl fluorides, 156 Electronic properties, SF compounds, 108-109 5



649 Electronic properties, vinyl fluoride, 156 Electrophilic fluorination asymmetric, benzylic fluorides, 182-183/ diastereoselective, toward allylic fluorides, 177-178 Electrophilicfluorodesilylationof allylsilanes in allylic fluoride synthesis, 177-178 Electrophilic halogenation, difluoroenoxysilanes, 384 Electrophilic peptide fragments, replicase turnover rates, 630/ Electrophilic perfluoroalkylation, overview, 3-8 Enamines, reactions chiral, with trifluoroacetaldehyde ethyl hemiacetal, 351 with polyfluoroacetaldehyde hemiacetal, 346-347/ with trifluoroacetaldehyde ethyl hemiacetal, 343-345 β-Enamino esters and iso(thio)cyanates in fluorinated uracil synthesis, 604-607 fluorinated, synthetic intermediates, 593-610 A -oxazoline protected, preparation, 598-599/ Enantiopure β-lactams, synthesis, 548-553 Enantioselective trifluoromethylation, 21-22, 79-82/ Endo/exo selectivity dependence in Diels-Alder reactions of vinyl fluorides, 158-159 5-Endo-trig cyclizations, 270-272 Engineeringfluorinatedcomb-like polymers, halogen bonding application, 537-538 Enol ethers-sulfur pentafluoro compounds, preparation, 95-96/ 2

Enolates, Michael addition reactions, 404-405 Enzymatic resolution, racemic C fluoroalkyl substituted amino acids, 612-615/ Epoxidation, application in asymmetric synthesis, 297-299/ Epoxides and aziridines, optically active trifluoromethylated, preparation, 323-324 Ester enolate condensation with fluorinated imidoyl halides or nitriles, 597-599 Ethyl bromodifluoroacetate effect of TMEDA in THF on Michael-type reaction, 483485 organocopper iodide complex formed in cross-coupling reaction, 478-481 organocopper reagent in Michaeltype reaction, 481-483 radical addition reaction mechanisms, 485-488 reaction mechanisms, 488-489 rhodium catalyzed reaction, 491— 492 Ethyl β-bromoperfluorocrotonate, 237 Evans oxazolidinone chiral auxiliary, 177-178 Explosives, SF compounds, 111-112 a

5

19

19

19

F labeled synthesis of trifluoromethyl ketones, 50-52 F NMR and N NMR spectra in N -I interaction, 524-525 F NMR determination, halogen bonding acceptor abilities, 527 F NMR spectra, three component systems, iodide halogen bonding strength, 529 14



650

Felkin-Anh and related transition state models in stereoselection, 405-407 Fiber reactive dye industry, industrial applications, 249 Fischer indole synthesis, Abramovitch adaptation, 306 Five-membered rings anodic fluorination heteroaromatic compounds, 279-280/ synthesis fluorinated heterocycles, 270-272 Flunarizine analog preparation, 69-70/ Fluoral iimniums, generation and uses, 67-72 Fluoral industrial synthetic application as fluorinated synthon, 368-376 Fluoral stable hemiaminals, use in trifluoromethylation, 63-66/ Fluoride salts (supporting) effect on selective anodic fluorination, 277-278/ Fluorinated acylsilanes, synthetic utility, 385-389 Fluorinated aliènes, functionalized, 204-215 Fluorinated allylic alcohol derivatives, disastereoselective cyclopropanation, 166 Fluorinated amides, Wittig reaction, 596 Fluorinated amino acids, synthesis, 562-571 Fluorinated β-amino acids, synthesis, fluorinated β-enamino esters reduction, 599-604/ 2-Fluorinated benzofurans, benzothiophenes, indoles, preparation by cyclization, 271 Fluorinated building blocks, synthesis, dienes and enynes with allylic fluorine, 179-180 Fluorinated cyclopropanecarboxylates, construction, 166

Fluorinated dianion equivalents, development, 466-469/ 2-Fluorinated dihydrofurans, dihydrothiophenes, pyrrolines, cyclization synthesis, 272 Fluorinated β-enaminoamides derivedfromchiral nonracemic acyclic and cyclic amides, 598 esters and iso(thio)cyanates, synthesis, fluorinated uracils, 604-607 esters A -oxazolin-C-protected, uracils prep, 607-609 esters reduction, synthesis fluorinated β-amino acids, 599-604/ esters synthetic intermediates, 593-610 Fluorinated imidoyl halides or nitriles, ester enolate condensation, 597599 3-Fluorinated isochromenes, preparation by cyclization, 265 3-Fluorinated isoquinoline derivatives, preparation by cyclization, 267269/ 3-Fluorinated isothiochromenes, preparation by cyclization, 265 Fluorinated β-keto esters and amines, condensation, 594-595 Fluorinated β-lactams, versatile synthetic building blocks, 554558 Fluorinated nitriles, ester enolate condensation, 599 Fluorinated peptidomimetics, synthesis and properties, 572592 Fluorinated prolines, syntheses, 563567 Fluorinated pyroglutamic acids, syntheses, 567-569 3-Fluorinated quinolines, preparation by cyclization, 266-267 2


651 3-Fluorinated quinolines with 2position substituents on quinoline ring, 269-270 Fluorinated silyl enol ethers, difluoromethylene/ monofluoromethylene groups, introduction, 49-52 Fluorinated uracils preparation from A -oxazolin-Cprotected β-enamine esters, 607-609 synthesis from β-enamino esters and iso(thio)cyanates, 604607 Fluorinated vinylzinc reagents, preparation, 135-154 Fluorination, biologically important imidazoles and indoles, 303316 Fluorine analogs, biologically important compounds, synthetic applications, 489-491/ Fluorine-based crystal engineering, 498-513 Fluorine-bromine addition to vinyl imidazoles, 309-310 Fluorine-containing methyl groups, role in diastereofacial selection, 399-411 Fluorine-effect in peptidomimetic structures, 573 Fluorine for peptide and protein modification, 611-635 Fluorine in aromatics, nucleophilic displacement, 292 1-Fluoro-1-alkenyl metals, synthesis, cross-coupling reactions, application, 124, 125-126, 127 Fluoro artemisinins, Lewis acidcatalyzed reactions, 459 2-Fluoro-2-aryl acetic acid derivatives, benzylic fluorides, resolution methods, 184 3-Fluoro-1,2-dihydroisoquinolines, preparation by cyclization, 266


2

1 -Fluoro-1 -haloalkenes, stereoselective synthesis, 121— 124, 125/ 2-Fluoro-1 -haloalkenes, stereoselective synthesis, 126, 127-132 Fluoro^-lactams, synthetic building blocks, 544-561 2-Fluoro-2-phenylalkanols, benzylic fluorides, resolution methods, 184 Fluoro segregation in crystalline phase, 501 Fluoro-substituted trifluoromethyldiarylsulfonium triflates, 7 Fluoro-taxoids, cytotoxicity, 558 a-Fluoro-a^-unsaturated carbonyl compounds in Diels-Alder reactions, 159-164 Fluoroalkyl/alkyl halides, sulfur pentafluoro-, preparation, 92-93 α-Fluoroalkyl amino acids incorporation into peptides, carboxypeptidase Y, 619-621 α-Fluoroalkyl amino acids incorporation into peptides trypsin and α-chymotrypsin, 616619 Fluoroalkyl groups, hydrogen bonding, 625 Fluoroalkylated alkynes, various syntheses, 191-193 a-Fluoroalkylphosphonates, 211-213 3-Fluorocinnolines, preparation by cyclization, 268 Fluorocyclopropanes, asymmetric synthesis, 184, 185/ Fluoroform. See Trifluoromethane 2- and 4-Fluoromethylimidazole, synthesis by deoxyfluorination, 308-309 Fluorophilic nature in crystal engineering, 501 Fluorophosphonates, isoacidic analogs, phosphates, 440



652 α-Fluorostyrene, asymmetric cyclopropanation, 168-169 Fluorovinylzinc reagents, in situ preparation at room temperature, 138-151 Free radical addition, direct introduction, difluoromethylenephosphonate unit, 445-446/ Free radical perfluoroalkylation, overview, 11-13 Friedel-Crafts asymmetric catalytic reactions, 362-366/ Friedel-Crafts asymmetric reaction, vinyl ether with fluoral gas, 369 Friedel-Crafts type catalytic enantioselective alkylation, trifluoropyruvate, 321 Functional group transformations at acarbon, trifluoromethyl group, 318-341

G Garner's aldehyde, in 4trifluoromethyl-D-proline synthesis, 563-564 Glyoxylate-ene reaction, application in asymmetric synthesis, 294295/ Grubbs catalyst, 72,418,435

H Halex (halogen exchange) fluorination, 263 Halocarbon HFC-134a in preparation and use of trifluorovinylzinc reagent, 139-145 Halogen bonded Ν—I formation, detection, 524-526 Halogen bonding

19

acceptor abilities, F NMR determination, 527 adducts with fluoroorganic derivatives, early studies, 516 based, crystal engineering, 514542 optical resolution, 324 Halogen dislocations, selection, 224, 226-227/ Halogen-halogen interactions in intermolecular synthons, 500 Halogen/pseudohalogen SF compounds, overview, 88-89 Halogenated aromatic compounds, regioexhaustive substitution, 219225 Halogenation of 2,2-difluoro enol silyl ethers, 50-52 Halogens, discrimination between seemingly equal, 224-225/ Halogens, heavy, deprotonationtriggered hopping, 223-224/ Haloperfluorocarbons, role in halogen bonding-based crystal engineering, 514-542 HCFC-133a, haloethane, preparation, a-chloro-P,P-difluorovinyl zinc reagent, 145-148 Heck reaction, 123, 124, 128-132/ 180 α-Helical coiled-coil peptides, melting temperatures, 629/ Hemiaminals of fluoral use in trifluoromethylation, 6366/ versatile reagents, 73-74/ Heteroaromatic compounds (5membered ring), anodic fluorination, 279-280/ Heterocycle chemistry, sulfur pentafluoro compounds, 102-103 Heterocycles, diastereoselective anodic fluorination, 284-286/ 5



653

Heterocycles from pentafluoropyridine, highly funetionalized, 248-255 Heterocyclic chalcogenium salts, 3-4 Heterocyclic compounds, selective anodic fluorination, 276-287 Hexatrifluoropropene trimer in fluorinated synthon, synthesis, 502-503 HFC-134a in preparation and use of trifluorovinylzinc reagent, 139— 145 Homoallyl trifluoromethyl amines, allylation reactions, 413-420/ Homochiral crystallization, 4,4,4trifluoro-3hydroxybutyrophenone, 370 Horner-Wadsworth-Emmons reaction, 120, 177-178,386-387/, 401 1,2-Hydride transfer mechanism, 372-373/ Hydroboration, fluoroalkylated alkynes, synthetic applications, 196-197 Hydrolysis/alcoholysis of JV-aeyl-βlactams, synthetic building blocks, 554-555 Hydrometallation, fluoroalkylated alkynes, synthetic applications, 193-197 Hydroperfluoroalkanes (RfH), 17 2-Hydroperfluorobutanoates, 5membered CF -heterocycles, synthesis, 243 a-Hydroperfluorocarboxylic derivatives, 235 Hydrostannation, fluoroalkylated alkynes, synthetic applications, 193-196 Hydroxide-induced trifluoromethylation, trifluoromethyl phenyl sulfones/sulfoxide, 36-41 3

a-Hydroxy-P-amino acids and esters, P-CF H- and P-CF -, synthesis, 554-555 3-Hydroxy-4-CF H-p-lactams, enantiopure, synthesis, 548-549/ 3-Hydroxy-4-CF -P-lactams, enantiopure, synthesis, 550-551, 553/ α-Hydroxy-a-methyl-P-amino acid, PCF -, synthesis, 554-556 a-Hydroxy-P-trifluoromethyl-P-amino acids, syntheses, 546-547 P-Hydroxy-P-trifluoromethylated ketones synthesis, 342-355 Hypervalent sulfuranide dioxide salts, synthesis, 28-29 2

3

2

3

3

Imidazoles, biologically important, selective fluorination, 303-310, 313-314 Imidoyl (fluorinated) halides, ester enolate condensation, 597-598/ Imines chiral, reaction with trifluoroacetaldehyde ethyl hemiacetal, 348-350/ reactions with polyfluoroacetaldehyde hemiacetal, 346-347/ reactions with trifluoroacetaldehyde ethyl hemiacetal, 345-346/ Iminiums, fluoral, generation and uses, 67-72 Imino (thio)ethers, intramolecular Wittig type rearrangement, 596597 Indium difluoroallenyl intermediate, 207208 mediated allylation reactions, 390-392



654 organometallic reagent in allylation reactions, 414 Indoleamines, ring-fluorinated, preparation, 306, 308/ Indoles, side chain fluorinated, preparation, 313 Infrared spectroscopy, detection, halogen bonded adduct formation, 525-526 Inorganic molecules, trifluoromethylations and perfluoroalkylations, 25-26 Intermolecular interactions, weak nonbonded, crystal engineering, overview, 499-500 Intermolecular nucleophilic reactions in stereospecific transformations, 329-330/ Intermolecular synthons, types of weak non-bonded interactions, 499-500 Intermolecular trifluoromethylation, trifluoroacetic and trifluoromethanesulfinic derivative, 75-76 Intramolecular nucleophilic substitutions in stereospecific transformations, 327-329/ Intramolecular trifluoromethylation, trifluoroacetic and trifluoromethanesulfinic derivative, 76-79 Intramolecular Wittig type rearrangement, imino (thio)ethers, 596-597 Iodide anion complex, interaction dissociation energy, 527 Iodide ion behavior in three component systems, 528531 Iodine and bromine, discrimination between, 224/ 226-227/ a-Iodo-P,P-difluorostyrenes, synthesis, 150-151/

lodoperfluoroalkenes, sulfur pentafluoro-substituted, preparation, 92 Ionic liquids, SF compounds, 112 IR. See Infrared spectroscopy Ireland-Claisen rearrangements, 400 Iron tricarbonyl-diene complexes in preparation, dienyl allylic fluorides, 179 Ishikawa's reagent, 401 Isoacidic analogs of phosphates, 440 Isoserine dipeptides, R containing, synthesis, 556-557/ Isoserine fluorinated analogs, Uneyama's synthesis, 601-602/ 5

r

Κ

Ketals and acetals, optically active trifluoromethylated, preparation, 323 Ketenes-sulfur pentafluoro compounds, preparation, 95-96/ 3-Keto-2,2-difluoro-lmethoxyiminiums, intermediates, 73,74/ γ-Keto α-perfluoroalkyl acid derivatives, 235

L Lanthanide-BINOL complexes in asymmetric epoxidation reactions, 297-299/ LDA. See Lithium diisopropylamide Lewis acid (boron) and S(perfluoroalkyl)dibenzothiopheni um triflate in perfluoroalkylation, 5 Lewis acid-catalyzed reactions, fluoro artemisinins, 459 Lewis acid mediators in Diels-Alder cycloadditions, 161-162



655 Lewis acid-promoted allylation reaction, 392-394/ Lewis acids, perfluroalkylation, metal enolates, 5 Librariesfromlibraries approach, 250-251 Lipase-catalyzed reactions, asymmetric synthesis, chiral gemdifluorocyclopropanes, 432-434/ Lipase-catalyzed transformations, optically active compound resolution, 184 Lipinski-type molecules, 250 Liquid crystals, application of halogen bonded halo-PFCs, 536-537 Liquid crystals, SF compounds, 112113 Lithium diisopropylamide (LDA), achloro-P,P-difluorovinyl zinc reagent, 146 Lithium diisopropylamide (LDA), generation, trifluorovinylzinc reagent, 142-144 5

M Magnesium metal-mediated reductive nucleophilic trifluoromethylation, 30-36 Magnesium organometallic reagent in allylation reactions, 414,418,421 Magnesium-promoted carbon-fluorine bond cleavage, 455-475 Magnesium-promoted selective defluorination aromatics, 462-463/ difluoromethyl ketones, 461-462 trifluoroacetates, 462 trifluoromethyl imines, 462 trifluoromethyl ketones, 458-461 MeCN. See Acetonitrile Meerwem-Ponndorf-Verley reduction in synthesis, anti-2,2difluoropropan-l,3-diols, 42

type reduction pathway, 38 Meisenheimer complexes, intermediates, 248 Melting point increase, indication of co-crystal formation, 517-518 Melting temperatures, α-helical coiled-coil peptides, 629/ Metal mediated allylation reaction in aqueous media, 389-392 Metal promoted coupling reaction, direct introduction, difluoromethylenephosphonate unit, 445 Metallations, permutational hydrogen/metal interconversions, 219-223/ Methoxycarbonylation reaction, 131— 132/ Methyl groups, fluorine-containing, role in diastereofacial selection, 399-411 1 -Methyl-2,2,2-trifluoroethylamine, enantiopure, synthesis, TFA and fluoral, 374-376/ (S)-a-Methyltrifluorolactic acid, synthesis using TCTFA, 373 Michael addition reactions, 400, 404409, 595 Michael-type reactions with ethyl bromodifluoroacetate effect of TMEDA in THF, 483485 organocopper reagent, 481483 Migita-Kosugi-Stille reaction, 195196/ See also Stifle coupling reaction Mitsunobu's conditions, 209 Molecular interactions, fluorinated amino acids with native polypeptides, 622-631 Molecular orbitals 1,6-bis(hydroxymethyl)-2,2,5,5tetrafluorobicyclopropane shape, 430-431



656 carbonyl carbon in carbonyl-ene reactions, 357-359* fluorinated compounds, 318320 trifluoromethylated carbanion, 332 Molybdenum-mediated intramolecular allene-alkyne cycloaddition, 209210 Monoalkyl substituted 1,1difluoroallenes, synthesis, 205 Monofluorinated compounds, asymmetric synthesis, 173-189 Monofluoroacetyltrialkylsilanes/mono fluoroenoxysilanes, synthesis, 383 Monofluoroacetyltrialkylsilanes reaction with sulfur ylides, 388389/ Monofluoroalkene stereoselective synthesis with cross-coupling reactions, 120-134 Monofluoroallenes, functionalized, 205-207,210-211 Monofluoroallenyl phosphonates, 211-213 Monofluoroenoxysilanes, synthesis, 383 Monofluoromethylene groups, introduction byfluorinatedsilyl enol ethers, 49-52 Monosubstituted SF benzene, efficient preparation method, 105-106 Mosher's acid, synthesis using TCTFA, 373-374 Mukaiyama-aldol reaction asymmetric, 360-362/ direct, trifluoroacetaldehyde ethyl hemiacetal with ketones, 351-353/ with 2,2-difluoro enol silyl ethers, 49/ Multi-gem-difluorocyclopropanes, synthesis, 434-437 5

Ν JV,#-Dimethylforniamide. See DMF Ν,Ν,Ν',Ν'Tetramethylethylenediamine. See TMED A Natural and \^[CH(CF )NH]Glypeptides, structure, 584/ Naturally occurring compounds, anti1,3-diol functionality as fundamental unit, 42 Nazarov cyclization, 2-butyl-l,ldifluoro-4-methyl-1,4-pentadien3-one, 487 Neutral electron donors, self-asembly, 515-526 Nitro-substituted trifluoromethyldiarylsulfonium triflates, 7 Nitrogen-iodine halogen bonding, role in self-assembly, 1-dimensional chains, 518-519 Nitrogen-iodine interaction, F and % NMR spectra, 524-525 Nitrogen-iodine interactions, trimeric adducts, TMEDA/iodoperfluoroheptane, 522-524 NMR F and N spectra in Ν—I interaction, 524-525 NMR F determination, halogen bonding acceptor abilities, 527 NMR F spectra, three component systems, iodide halogen bonding strength, 529 Nuclear magnetic resonance. See NMR entries Nucleophilic addition, direct introduction difluoromethylenephosphonate unit, 442 Nucleophilic aromatic substitution in pentafluoropyridine, 249 Nucleophilic conjugate addition, direct introduction 3

l9

19

14

I9

l9



657 difluoromethylenephosphonate unit, 443-444 Nucleophilicfluoridationsin benzylic position, 181 Nucleophilic fluoroalkylation chemistry, 16-56 Nucleophilic perfluoroalkylation, overview, 8-11 Nucleophilic substitution direct introduction difluoromethylenephosphonat e unit, 442-443/ on carbonyl groups, 444 stereospecific, in atrifluoromethylated carbinol unit, 325-327 See also S 2 entries Nucleophilic trifluoromethylation, new methodologies, 59-82

Organocopper reagent and ethyl bromodifluoroacetate, Michaeltype reaction, 481-483 Organometallic reagents, unsaturated, reactions on trifluoroacetaldimines, 412-428 A -Oxazolin-C-protected β-enamine esters influorinateduracils prep, 607-609 1,3-Oxazolidine, diastereoselective anodicfluorination,284 Oxazolidinone auxiliary in chemoselective cleavage, pseudopeptides, 580 Oxygen—iodine halogen bonding, role in self-assembly process, 520-522 2

N

Ο

Ochiai's method, 130 Olefin metathesis reaction protocol, multi-gem-difluorocyclopropanes, 435-437 Olefination reactions, fluorinated acylsilanes, 385 Olefinic bond, reactivity range, 93 Optically active compound resolution, lipase-catalyzed transformations, 184 Optically active gemdifluorocyclopropanes, synthesis, 432-434/ Optically active trifluoromethylated compounds, preparation, 320324 Organic derivatives-SFsfromprimary and secondary synthons, preparation, 91-108 Organocopper iodide complex formed in cross-coupling reaction, 478481

P-K reaction. See Pauson-Khand reaction Palladium catalyst in primary phosphonate preparation, 445 Palladium catalyzed coupling a-chloro-P,p-difluorovinyl zinc and iodobenzene, 146 fluoroalkylated acetylides with halides, 191-192 fluorovinylzinc reagents with aryl or vinyl halides, 137, 139/ Sonogashira-type reactions, 253254,255 Palladium-catalyzed methodology, side-chain homologation, 208209 Panomifene synthesis, antiestrogenic drug, 201-202/ Partially modified retro. See PMR Pauson-Khand (P-K) reaction, 209 Pentafluoropyridine in synthesis, functionalized heterocycles and macrocycles, 248-261 Peptides, ψ[€Η(€Ρ )ΝΗ]01νpeptides, 584-587/ 3


658 Peptidomimetic metalloproteinase inhibitors, trifluoro-analogs, 573577 Peptidomimetics, fluorinated, synthesis and properties, 572592 Perfluorinated blood substitute, SF compounds, 111 Perfluoro-4-isopropylpyridine building block for macrocycle synthesis, 256-257 Perfluoro-4-isopropylpyridine reactions, summary, 252/ Perfluoroaldehydes, thioacetalization, 233-234/ Perfluoroalkyl iodides sulfur pentafluoro-, preparation, 91-92 with aromatic and aliphatic diamimes, co-crystal formation, 516-517/ α-Perfluoroalkyl succinic acid derivatives, 236-237/ Perfluoroalkylation methodology, recent advances, 2-15 Perfluorodithiocarboxylic esters, thiophilic organometallic addition-elimination, 234 Perfluoroketene dithioacetals, 232247 1,4-Perfluoromethylation, 24-25 Perfluoromethylation with (trifluoroalkyl)trimethylsilanes (TMSRf), 18-21 Permutational halogen/metal interconversions, 223-225/ 2-Phenyl-l,l,2-2tetrafluoroethanesulfonic acid, synthesis, 51, 52/ Phenyl trifluoromethanesulfonate, trifluoromethylation, 28-29 Phosphonates, monofluoroallenyl, 211-213 Photo induced reduction, CF I, 10


5

3

π -Systems, selective monofluorination in vicinal position, 173-189 Plasma etching gas, SF compounds, 112 5

PMR ψ[ΝΗ0Η(0Ρ )]Ο^-ρ6ρίΐά68, 3

581-584 PMR y[NHCH(CF )]Gly-peptidyl hydroxamates, solid-phase synthesis, 581-582 PMR y[NHCH ]-peptides with 3,3,3trifluoroalanine mimic, synthesis, 589 Polyester derivatives-sulfur pentafluoro compounds, preparation, 100 Polyfluorinated BINOLs application in asymmetric catalysis, 293-299/ regioselective nucleophilic aromatic substitution, fluorine, 291-292 Polyfluorinated moieties, new reagents for introduction, 5786 Polyfluoroalkylaldehyde hemiacetal, reactions with enamines and imines, 346-347/ Polysubstitution in pentafluoropyridine, orientation, 251/ Polyunsaturated and dienyl allylic fluorides, preparation, 179-181 Porphyrins, direct trifluoromethylation, 5 Potassium /er/-butoxide induced trifluoromethylation, 37-41 Power-variable electrophilic perfluoroalkylating agents, 4 3

2

Privileged structures strategy, 250

Proline-catalyzed direct aldol reaction with ketones, 351-353/ Prolines,fluorinated,syntheses, 563567



659 Propargylie fluorides intermediates, fluorinated allylic building blocks, 178 optically active, synthesis, 174175 Protease catalyzed peptide synthesis, α-fluoroalkyl amino acids into peptides, 615-621 Protease inhibitors, fluorine containing, 421 "Protect-in-situ" methodology in 1,4trifluoromethylation, 25/ Pyridine derivatives, highly substituted, synthesis, 249-255 Pyroglutamic acids, fluorinated, syntheses, 567-569 Pyrrole derivative, anodic ring fluorination, 281-283/

R Racemic C^-fluoroalkyl substituted amino acids, enzymatic resolution, 612-615/ Radical addition mechanisms, conformation effects, 486-487/ Radical addition reaction mechanisms, routes to CF compounds, 485488 Radical reaction, α,α-difluoro fatty acid analog synthesis, 490-491/ Raman spectroscopy, detection, halogen bonded adduct formation, 525-526 Rapid analogue synthesis (RAS), 250251 Reactive species in regioselective trifluoromethylation, CC1 +, 7-8 Reagent-controlled optional site selectivity, metallations, 220-221 Recystallization for optical purification, trifluoromethylated carbinols, 320 2

3

Reductive dechlorofluorination, difluorinated enol ethers and derivatives, 457 Reductive trifluoromethylation, 30-36 Reformatsky reaction, 73, 477-478 Reformatsky-type reaction in difluorinated enol ethers and derivatives, preparation, 456 Refrigerant fluids, SF compounds, 112 Regioexhaustive fiinctionalizations, 218-231 Regioexhaustive substitution, halogenated aromatics, "toolbox methods," 219-225 Regioselective trifluoromethylation, 7-8 Replicase reaction cycle, 625 Resolution, racemic mixtures via diastereoisomeric adducts, halogen bonding, 532-534 Retro and retro-inverso ψΙΝΗΟΗ^ΜΟΙν-ρβρηάββ, partially-modified, 577-584 Retro-Diels-Alder reaction, 213. See also Diels-Alder reaction Retro-inverso. See Retro entry Reversed disorder structure in crystal packing,fluorohybrid synthons, 504-505 Rhenium complexes in stereospecific fluorination, allylic alcohols, 176-177 Rhodium catalyzed reaction, ethyl bromodifluoroacetate, 491-492 Rhodium salts, catalyst for construction, fluorinated cyclopropanecarboxylates, 166 Ring closing metathesis, iV-allyl homoallyl amines, 418,420/ Ring closing metathesis, diastereoselective prep, 7-member β-amino acid derivatives, 602604 5



660 Ring closure rules, proposed by Baldwin, 209 Ring-fluorinated heterocycles, preparation, intramolecular vinylic substitution, 262-275 Ring-fluorinated heterocycles (5membered ring), synthesis, 270272 Ring-fluorinated heterocycles (6membered ring), synthesis, 265270 Ring-fluorinated imidazoles, preparation, 305-306 Ring-fluorinated indoleamines, preparation, 306, 308/ Ring opening coupling N-acyl-βlactams with amino esters, 556557/ Ring opening coupling JV-acyl-βlactams with baccatins, 557-558* Ring opening hydrofluorination, arylglycidic esters, 181-182 Ring opening regioselective, in methanolyses, 374 "Rules of 5," 250 Ruppert-Prakash reagent, 79. See (Trifluoromethyl)trimethylsilane Ruthenium complex catalyzed-olefm metathesis reaction protocol, 435-436 organometallic catalyst in ring closing metathesis, 418,420* oxide in oxidation, fluorinated proline derivatives, 567-568/

Schlenk equilibrium, mono and bis zinc reagent, 144/ Screening system application to amino acids carryingfluorinatedside chains, 625-631 coiled coil based, 623-625 Selenium-(perfluoroalkyl)dibenzothiosalts, 4 Self-assembly anionic electron donors, 526532 neutral electron donors, 515-526 three component systems, 528/ SF -aliphatic hydrocarbons, preparation, 94-95 SF -alkyl/fluoroalkyl halides, preparation, 92-93 SF -carboxylic acids, acid halides, esters, salts, preparation, 97-100 SF compounds, aromatic and heterocycle chemistry, 102-108 SF compounds, polymer chemistry, 100-102 SF compounds, properties and applications, overview, 108-113 SF -organic derivativesfromprimary and secondary synthons, preparation, 91-108 SF -oxygen-containing compounds, preparation, 95-96/ SF -perfluoroalkyl iodides, preparation, 91-92 SF -sulfur-containing compounds, preparation, 95-96/ SF -system intermediates, overview, 89-91 SF X in syntheses, organic derivatives of sulfur hexafluoride, 87-118 See also Sulfur hexafluoride Shapiro reaction in synthesis, monoalkyl substituted 1,1difluoroallenes, 205 Side-chainfluorinatedimidazoles, preparation, 307-312/ 5

5

5

5

5

5

5

5

5

5

5

S

5

Sakurai-type allylation, 392-394/ Saquinavir, HIV-1 protease inhibitor, 421 Schiemann reaction, 2- and 4fluorinated imidazole derivatives, 304-305/



661 Side-chainfluorinatedurocanic acids, preparation, 310-312 Silyl enol ethers fluorinated, difluoromethylene and monofluoromethylene group introduction, 49-52 with fluoral, asymmetric FriedelCrafts reactions, 362-364/ Simmons-Smith reaction in diastereoselective cyclopropanations, 166 Simple inorganic molecules, perfluoroalkylations and trifluoromethylations, 25-26 Site protective groups, deployment, 221-223, 227-229/ Six-membered ring-fluorinated heterocycles, synthesis, 265-270 S 2 strategy in stereospecific transformations, 330-331 S 2'-type reactions, difluorinated enol ethers and derivatives, preparation, 457-458/ S 2'-type reactions. See also Nucleophilic substitution S V process, nucleophilic substitution, vinylic fluorine, 263-264/ Sodium borohydride, deprotection reactions isoserine fluorinated analogs, 602 Sodium methoxide-induced trifluoromethylation, 38 Solid-state synthesis application of hybrid PFC-HC materials, 534-535 PMR ψ[ΝΗΟΗ(ΟΡ )]Θ^peptides, 581 PMR ψ[ΝΗ0Η(€Ρ )]Ο1νpeptidyl hydroxamates, 581582 Solid-state UV-initiated polymerization, fluoro synthons, 508-510 f

N

N

N

N

3

3

Solvent effects in aza-Michael reaction, 579, 585 on anodicfluorination,278-280/ rhodium catalyzed ethyl bromodifluoroacetate reaction, 491 Solvents for highly fluorinated polymers, SF compounds, 111 Sonogashira-type coupling reactions, 123-124, 128-129, 132, 180,201, 253-254, 255 2-Spirocyclohexyl-1,3-dioxolan-4-yl group, effect on diastereoselectivity, 285 Stabilization strategies for trifluoromethyl anion, overview, 59-60 Stannane. See Tin Staudinger reaction, 547 Stereocontrolled alkylations, trifluoromethylated chiral carbon center, 322-323 Stereocontrolled oxidations, trifluoromethylated chiral carbon center, 322 Stereocontrolled reductions, trifluoromethylated chiral carbon center, 321,322 Stereocontrolled synthesis, Tfm-malic framework, 574-575/ Stereoselection in diastereoselective enolate Michael addition reactions, 405-409 Stereoselectivefluorinationin synthesis chiral, non racemic allylic fluorides, 176-177 Stereoselective methylation, jV-acyl-βlactam, 554-556 Stereoselective synthesis, monofluoroalkenes, crosscoupling reactions, 120-134 Stereospecific transformation, functional groups on α-carbon to trifluoromethyl group, 325-333 5



662 Stille coupling reaction, 122, 124, Tellurium131-132/ 192. See also Migita(perfluoroalkyl)dibenzothiosalts, Kosugi-Stille reaction 4 Structural unit variation, pyridine 1,1,1,2-Tetrafluoroethane. See HFClinking in macrocycles, 257-258 134a Substrate and medium engineering, α· Tetrahydrofuran. See THF fluoroalkyl amino acids into Tetrakis(dimethylamino)ethylene peptides, 616-619 (TDAE), 17 Sulfides, oxidation to sulfoxides, Tetramethylethylenediamine. See application in asymmetric TMEDA synthesis, 293 TFA, industrial synthetic application Sulfinimines, diastereoselective asfluorinatedsynthon, 369/ 374trifluoromethylation, 18-21 376/ Sulfur-carbon bond cleavage reactivity Tfm-hydroxamates, syntheses, 574compared to deprotonation 577 reactivity, 43, 45/ TFS. See α,β,β-Trifluorostyrene Sulfur hexafluoride, 88. See also SF$X Thermal stability, SF compounds, entries 110 Sulfur hexafluoride, organic Thermal unfolding profiles, ligated derivatives, SF X materials in coiled coil peptides, 628/ syntheses, 87-118 THF (Tetrahydrofuran) Sulfur-(perfluoroalkyl)dibenzothioalternative solvent, 33 solvent for allylation reaction, salts, 3-4 414-415t Supportingfluoridesalts, effect on solvent in metal mediated selective anodic fluorination, allylation reactions, 390 277-278/ Surface activity, SF compounds, 110 solvent with CF reservoir, 61-63/ Surrogate-unit strategy, 578 Thiazolines, Af-protected, Suzuki coupling conditions, 211 diastereoselective anodic Suzuki-Miyaura coupling reactions, fluorination, 284 122-123,129-130,133,196-197, Thioketone trifluoromethylation, 26201 27 π -Systems, selective Thioketones-SF compounds, monofluorination in vicinal preparation, 95-96/ position, 173-189 Three component systems, selfassembly, 527-532/ Tin stannane intermediates, dienes and enynes with allylic Taxoid anticancer agents, CF H- and fluorine, 179-180/ CF -containing, synthesis, 557tributyltinhydride/initiator, 558* secondary phosphonate TCTFA, industrial synthetic synthesis, 446 application as fluorinated vinylstannanes, synthetic building synthon, 369/ 372-374 blocks, preparation, 193-196/ 5

5

5

3

5

2

3



663 Titanium catalysis in Friedel-Crafts reaction, asymmetric synthesis, 295-296/ Titanium tetrachloride catalyst, N-acyl-oxazolin-2-thione with ethyl trifluoropyruvate, 574-575 in perfluoroaldehyde thioacetalization, 233-234/ mediator in Diels-Alder cycloadditions, 161-162 promoted allylation reaction, 392-394/ 395 Titanium-trifluoromethyl complexes, preparation, 29/ TMEDA and iodoperfluoroheptane, Ν—I interactions leading to trimeric adducts, 522, 523-524 TMEDA in THF, effects on Michaeltype reaction, ethyl bromodifluoroacetate, 483-485 TMSCF in trifluoromethylation with trimethylamine TV-oxide catalyst, 22-24 Toolbox methods tool selection, 225-229/ 2 x 3 , regioexhaustive substitution, halogenated aromatic compounds, 219— 225 Transition metal perfluoroalkyl complexes, synthesis, 29 Transmetallation mechanism, isomerization, 219-220 Trialkoxyboranes, perfluoroalkylations and trifluoromethylations, 28 Trialkyl boron in SF C1 addition to olefins, 93 Trialkylsilyl vs. chlorine, protective groups comparison, 227-229/ 2,4,6-Tribromo-3,5-difluoropyridine, reactions, 253/ 3,3,3 -Trichloro-1,1,1 -trifluoroacetone. See TCTFA 3

5

4,4,4-Trifluoro-2,3-epoxybutyric acid ethyl ester, synthesis, 371-372/ 4,4,4-Trifluoro-3-hydroxybutyric acid derivatives, enantiopure, synthesis, 369-372 Trifluoroacetaldehyde ethyl hemiacetal, in (ï-hydroxy-βtrifluoromethyl ketone prep, 342355 Trifluoroacetaldehyde hemiacetal, trifluoromethylating agent, 8-9 Trifluoroacetaldimines, reactions with unsaturated organometallic reagents, 412-428 Trifluoroacetates, magnesiumpromoted selective defluorination, 462 Trifluoroacetic and trifluoromethanesulfinic derivatives, trifluoromethylation, 75-82 1,1,1 -Trifluoroacetone. See TFA Trifluoroacetyltrialkylsilanes, synthesis, 384-385/ Trifluoroacylsilanes, synthesis, 379380/ 3,3,3-Trifluoroalanin incorporation into peptide sequence, 587-589 2,2,2-Trifluoroethyl phenyl sulfide, sulfoxide, and sulfone, reactions, 35/ Trifluorolactic acid derivatives, synthesis with DCTFA and TCTFA, 372-374 Trifluoromethane, 17, 60-63 Trifluoromethanesulfinic and trifluoroacetic derivatives, trifluoromethylation, 75-82 iV-Trifluoromethanesulfinyl-N'benzylpiperazine reagent, 7576/ Trifluoromethyl allyl amines, preparation, 418,421-424 Trifluoromethyl anion stabilization, overview, 59-60



664 5-Trifluoromethyl l,2-dithiole-3thione, trifluoromethylated heterocycles synthesis, 243 P-Trifluoromethyl-a,p-enones, Econfiguration, preparation, 6769 Trifluoromethyl epoxide, diaminopropanol precursor, preparation, 422 2-Trifluoromethyl furans and pyrroles, trifluoromethylated heterocycles, 241-242/ Trifluoromethyl group, functional group transformations at acarbon, 318-341 Trifluoromethyl homoallylic amines, allylation reactions, 413-420* Trifluoromethyl imines, magnesiumpromoted selective defluorination, 462 Trifluoromethyl iodide, 17 Trifluoromethyl ketones, F-labeled synthesis, 50-52 Trifluoromethyl ketones, magnesiumpromoted selective defluorination, 458-461 ot-Trifluoromethyl γ-lactams, trifluoromethylated heterocycles synthesis, 238-239 2-Trifluoromethyl γ-lactones, trifluoromethylated heterocycles synthesis, 238 Trifluoromethyl phenyl sulfone/sulfoxide and sulfide, Mg° mediated trifluoromethylation, 30-36 Trifluoromethyl phenyl sulfone/sulfoxide in alkoxideinduced trifluoromethylation, 3641 4-Trifluoromethyl proline syntheses, 563-566 Trifluoromethyl pyrazoles and pyrimidines, trifluoromethylated heterocycles, 242 l8

4-Trifluoromethyl pyridazine derivatives, trifluoromethylated heterocycles, 239-240/ Trifluoromethyl trimethylsilane. See TMSCF Trifluoromethylated acetylenes, onepot synthesis, 192-193/ γ-Trifluoromethylated allylalcohols in S 2* type reaction, 330-331 Trifluoromethylated amines, optically active, preparation, 322 Trifluoromethylated carbanion chemistry, 331-333/ Trifluoromethylated carbinols, optical purification, 320 Trifluoromethylated chiral carbon center, construction, 320-324 Trifluoromethylated heterocycles, synthesis bis(ethylsulfanyl) hexafluorobutene line, 241245 bis(ethylsulfanyl)tetrafluoropropene line, 238241 Trifluoromethylated propargylic amines, preparation, 424-425/ Trifluoromethylation chiral substrates, 79-82/ phenyl trifluoromethanesulfonate, 28-29 with hemiaminals of fluoral, 6366/ with S-CF , sulfonium salts, kinetic study, 7 with trifluoroacetic and trifluoromethanesulfinic derivatives, 75-82 with trifluoromethane generation, 60-63 with trifluoromethyl phenyl sulfone, sulfoxide and sulfide, 30-41 with (trifluoromethyl)^^ (TMSCF ), 18-21 3

N

3

3



665

with trimethylamine TV-oxide catalyst, 22-24 Trifluoromethylation and perfluoroalkylation, trialkoxyboranes, 28 Trifluoromethylation and perfluoroalkylation, inorganic molecules, 25-26 Trifluoromethyldiarylsulfonium triflates, 7 Trifluoromethyloxonium salts, reactions, 5-7 Triflluoromethylsilane, catalytic production pathway, 35-36/ Trifluoromethylsilanes, preparation, Mg°-mediated reductive cleavage of C-S bonds, 31-33 2-Trifluoromethylsuccinimides, trifluoromethylated heterocycles synthesis, 240-241 Trifluoromethyltrimethylsilane (TMSCF ), in trifluoromethylation, 18-21 α,β,β-Trifluorostyrenes (TFS), synthesis, 139-145/ Trifluorovinylzinc reagent from halocarbon HFC-134a, in situ preparation/use, 139-145 Trimeric adducts of TMEDA and iodoperfluoroheptane, Ν—I interactions, 522, 523-524 Trimethylamine TV-oxide catalyst in trifluoromethylations, 22-24 Trisubstituted SF benzene derivative, preparation, 104 Tris-SF carbon compounds, 9495 Trypsin and α-chymotrypsin, afluoroalkyl amino acids into peptides, 616-619 Trypsin-catalyzed peptide synthesis, C ,a-dialkylated amino acids, 618/ Tyramine oxidase inhibitor, 166 3

5

U Ullmann coupling, 291 Uneyama's synthesis, isoserine fluorinated analogs, 601-602/ Uracil syntheses from β-enamino esters and iso(thio)cyanates, 604-607 ring-opening reaction of pyrimidinones, 608 Urocanic acids, side-chain fluorinated, preparation, 310-312 UV-initiated photopolymerizations, diacetylene functionalized fluoro synthons, 508-510

V

Vibrindole analogs, preparation, 70, 71/ Vinyl ether with fluoral, asymmetric Friedel-Crafts reactions, 364 Vinyl fluorides cyclopropanations, 164-170 in cycloadditions, 155-172 in Diels-Alder reactions, 157-164 Vinyl halide metallation in preparation offluorovinylzincreagents, 136 Vinyl imidazoles, addition of "FBr," 309-310 Vinylicfluorine,nucleophilic substitution by S V process, 263264/ N

5

a

W Water, solvent in metal mediated allylation reactions, 389-392 Weak hydrogen bonding in intermolecular synthons, 500 Wilkinson catalyst in ethyl bromodifluoroacetate reaction, 491-492


666 Wittig reaction, 180 difluoroacetyltrialkylsilanes, 386, 394 fluorinated amides, 596 Wittig type intramolecular rearrangement, imino (thio)ethers, 596-597


X X-ray crystallographic analysis macrocycles, 257/ 258-259/ Michael addition products, stereochemistry determination, 404-405

Ζ Zinc

fluorovinylzinc reagents, in situ preparation at room temperature, 138-151 insertion intofluorinatedvinyl halides, fluorovinylzinc reagents, 136,137,138/ organometallic reagent in allylation reactions, 414419 organozinc reagent, phosphonate synthesis, 445 powder in Michael-type 1,4 addition reactions, 483 promoted allylation reactions, 391-392 Zinc chloride-TMEDA, in fluoroalkylated alkyne synthesis, 192 Zinc/cobalt(III) bimetallic redox system, primary phosphonates synthesis, 445

diethyl, and rhodium catalyst, ethyl bromodifluoroacetate reaction, 491-492


Fluorine-Containing Synthons

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